Review: changing (shared) heritability of ASD and ADHD across the lifespan
Eur Child Adolesc Psychiatry
Review: changing (shared) heritability of ASD and ADHD across the lifespan
Nanda N. J. Rommelse 0 1 2
Catharina A. Hartman 0 1 2
0 Department of Psychiatry, Interdisciplinary Center of Psychopathology and Emotion Regulation (ICPE) and Research School of Behavioral and Cognitive Neuroscience, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands
1 Karakter, Child and Adolescent Psychiatry University Center , Nijmegen , The Netherlands
2 Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center , Nijmegen , The Netherlands
3 Nanda N. J. Rommelse
been strongly focused on childhood. The age of onset for ASD and ADHD is nearly always in childhood ([18]; but see [17]), which is the likely reason for this bias. However, given that it is already well known that developmental changes take place in both ADHD and ASD symptom domains separately, a focus beyond childhood is needed to further understand the potentially changing etiology of ADHD-ASD co-occurrence.
Introduction
Autism spectrum disorder (ASD) and attention-deficit/
hyperactivity disorder (ADHD) frequently co-occur. In
clinical practice, we daily struggle deciding if one, or the
other, or both disorders, best describe the child’s
problems. A strong body of literature has convincingly shown
that large overlap exists regarding genetic factors [
6, 11,
26, 29
]. However, this genetic overlap may significantly
depend on age. It is well known that genetic influences
on behavior are not at all constant during development
and continuously co-act and interact with
environmental factors influencing behavioral functioning [
1, 30
]. For
example, increasing heritability can result from
amplification, whereby early genetic influences become stronger
across time. As a second example, genetic influences may
be stable; yet novel genetic influences may emerge with
time while early genetic influences may decrease [
2
].
Despite everyone’s awareness of change in the (genetic)
mechanisms underlying the development of an individual
until elderly age in typical development, studies on
neurodevelopmental disorders like ADHD and ASD have
Several longitudinal twin studies on ADHD symptoms report
that new, age-specific genetic effects influence ADHD
symptoms in adolescence and adulthood, suggesting that ADHD
symptoms are a developmentally complex phenotype
characterized by both continuity and change across the life span [
3,
9, 12, 13, 19
]. In addition, only a modest overlap between
longitudinal genetic effects underlying both symptom domains
(inattention versus hyperactivity/impulsivity) appears present,
suggesting it is necessary to study both separately.
Moreover, several longitudinal studies report that subgroups may be
formed based on various combinations of symptoms in both
domains across the longitudinal course that likely has partly
distinct genetic underpinnings ([
7, 14, 25
]). These findings
strongly suggest that genetic effects implicated in childhood
ADHD may not at all be directly comparable to those that
influence ADHD in adulthood. This concurs with a review on
molecular genetics in adult ADHD, where it was concluded
that only some genes potentially related to childhood ADHD
have been replicated in adults with the disorder [
8
]. In
addition, in some cases the same genes were implicated, but
different alleles increased the risk for ADHD in children versus
adults (for instance, the 10-repeat in the dopamine transporter
gene [DAT1] increased the risk for ADHD in children, but
decreased the risk in adults) [
8
]. Note though that currently
there are no unequivocal molecular genetic findings for
ADHD in either childhood or adulthood, possibly
contributing to these results. Moffitt et al. [
17
] reported about adults
aged 38 years presenting with an ADHD symptom picture,
who did not have childhood ADHD as assessed in early
adolescence. They did not share the genetic and
neuropsychological alterations of those who did have the childhood
diagnosis. Even during adolescence, environmental effects (like
smoking) controlled for genetic confounders may have a
significant impact on future development of ADHD symptoms
[
33
], illustrating the developmentally sensitive nature and
non-static genetic influence of the ADHD phenotype beyond
childhood.
Heritability of ASD across the life span
In comparison to ADHD, fewer longitudinal, genetically
informative studies have examined the developmental
nature of ASD symptoms into adolescence or even
adulthood. Specifically, studies on the presence of new genetic
effects occurring in late adolescence or adulthood
compared to childhood—as reported for ADHD—have not
yet been conducted. In addition, to what extent the
different symptom domains of ASD are influenced by distinct
genetic effects over time is unknown. A study reporting on
the stability of genetic effects from childhood into early
adolesce (...truncated)